The genome sequence of the plant pathogen Xylella fastidiosa. The Xylella fastidiosa Consortium of the Organization for Nucleotide Sequencing and Analysis

Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis--a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We can assign putative functions to 47% of the 2,904 predicted coding regions. Efficient metabolic functions are predicted, with sugars as the principal energy and carbon source, supporting existence in the nutrient-poor xylem sap. The mechanisms associated with pathogenicity and virulence involve toxins, antibiotics and ion sequestration systems, as well as bacterium-bacterium and bacterium-host interactions mediated by a range of proteins. Orthologues of some of these proteins have only been identified in animal and human pathogens; their presence in X. fastidiosa indicates that the molecular basis for bacterial pathogenicity is both conserved and independent of host. At least 83 genes are bacteriophage-derived and include virulence-associated genes from other bacteria, providing direct evidence of phage-mediated horizontal gene transfer.     

Constructing dystopian experience: A Neurath-Cartwrightian approach to the philosophy of social technology

Social situations, the object of the social sciences, are complex and unique: they contain so many variable aspects that they cannot be reproduced, and it is even difficult to experience two situations that are alike in many respects. The social scientists' past experiences that serve as their background knowledge to intervene in an existent situation is poor compared to what a traditional epistemologist would consider ideal. A way of dealing with the variable and insufficient background of social scientists is by means of models. But, then, how should we characterize social scientific models? This paper examines Otto Neurath's scientific utopianism as an attempt to deal with this problem. Neurath proposes that social scientists work with utopias: broad imaginative plans that coordinate a multitude of features of a social situation. This notion can be used in current debates in philosophy of science because we notice that utopias, in Neurath's sense, are comparable to models and nomological machines in Nancy Cartwright's conception. A model-based view of science lays emphasis on the fact that scientists learn from the repeated operation of such abstract entities, just as they learn from the repetition of experiments in a laboratory. Hence this approach suggests an approximation between the natural and the social sciences, as well as between science and utopian literature. This is exemplified by analyzing the literary dystopia We, written by Yevgeny Zamyatin, to show that reasoning from and debating about utopian writings, even if fictional and pessimistic, creates phenomena of valuation, which are fundamental for constituting a background of experiences in the social sciences.     

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.     

EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa

Using a positional cloning approach supported by comparative genomics, we have identified a previously unreported gene, EYS, at the RP25 locus on chromosome 6q12 commonly mutated in autosomal recessive retinitis pigmentosa. Spanning over 2 Mb, this is the largest eye-specific gene identified so far. EYS is independently disrupted in four other mammalian lineages, including that of rodents, but is well conserved from Drosophila to man and is likely to have a role in the modeling of retinal architecture.     

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10?? to P = 1.8 × 10???) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10?3 to P = 1.2 × 10?13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.     

Landscape of transcription in human cells

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.     

Highly specialized mammalian skulls from the Late Cretaceous of South America

Dryolestoids are an extinct mammalian group belonging to the lineage leading to modern marsupials and placentals. Dryolestoids are known by teeth and jaws from the Jurassic period of North America and Europe, but they thrived in South America up to the end of the Mesozoic era and survived to the beginnings of the Cenozoic. Isolated teeth and jaws from the latest Cretaceous of South America provide mounting evidence that, at least in western Gondwana, dryolestoids developed into strongly endemic groups by the Late Cretaceous. However, the lack of pre-Late Cretaceous dryolestoid remains made study of their origin and early diversification intractable. Here we describe the first mammalian remains from the early Late Cretaceous of South America, including two partial skulls and jaws of a derived dryolestoid showing dental and cranial features unknown among any other group of Mesozoic mammals, such as single-rooted molars preceded by double-rooted premolars, combined with a very long muzzle, exceedingly long canines and evidence of highly specialized masticatory musculature. On one hand, the new mammal shares derived features of dryolestoids with forms from the Jurassic of Laurasia, whereas on the other hand, it is very specialized and highlights the endemic, diverse dryolestoid fauna from the Cretaceous of South America. Our specimens include only the second mammalian skull known for the Cretaceous of Gondwana, bridging a previous 60-million-year gap in the fossil record, and document the whole cranial morphology of a dryolestoid, revealing an unsuspected morphological and ecological diversity for non-tribosphenic mammals.     

Rosette formation by human T and B lymphocytes in the presence of adrenergic and cholinergic drugs

Summary It was shown that adrenergic drugs, which increase the intracellular levels of cAMP, inhibit the rosette formation by T-lymphocytes, but stimulate the rosettes produced by B-lymphocytes. Cholinergic drugs, which increase the levels of cGMP, on the contrary, stimulate the formation of rosettes by T-lymphocytes but inhibit those produced by B-lymphocytes.Acknowledgments. This investigation was supported by Grant from National Council for Scientific and Technological Development (CNPq), Rio de Janeiro, Brazil.     

Effects of alcohol ingestion on adrenergic nerve endings of rat atrioventricular valves

Zusammenfassung Bei Ratten, die während 4 Monaten ad libitum 40% igen Zuckerrohrschnaps getrunken hatten, wurden tiefgreifende Degenerationserscheinungen des adrenergischen Nervenplexus der Atrioventrikularklappen festgestellt.

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At the time of this investigation J.C.M.S. was holder of a fellowship of the Conselho Nacional de Pesquisas.